Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-Chronic Obstructive Pulmonary Disease? A Prospective, Population-based Cohort Study.

Rationale: The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than -1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings.

Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.

Risk factors and clinical characteristics of breathlessness in Australian adults: Data from the BOLD Australia study.

BACKGROUND: Breathlessness is a common symptom related to a significant health burden. However, the association of breathlessness with clinical characteristics, especially objective pulmonary test results is scarce. We aimed to identify the characteristics independently associated with breathlessness in Australian adults. METHOD: The analysis used data from BOLD Australia, a cross-sectional study that included randomly selected adults aged ≥40 years from six sites in Australia. Clinical characteristics and spirometry results were compared for breathlessness (modified Medical Research Council [mMRC] grade ≥2). RESULTS: Among all respondents (n = 3321), 252 participants (7.6%) reported breathlessness. The main univariate associations were obesity, chronic respiratory diseases, heart diseases and being Indigenous Australians (odds ratios [ORs] = 2.78, 5.20, 3.77 and 4.38, respectively). Participants with breathlessness had lower pre-and post-bronchodilator lung function than those without. Impaired spirometry results including FVC or FEV1 below 80% predicted, or FEV1/FVC < LLN were independently associated with breathlessness (adjusted ORs = 2.66, 2.94 and 2.34, respectively). CONCLUSIONS: Breathlessness is common among Australian adults and is independently associated with obesity, chronic respiratory diseases, heart diseases, being Indigenous Australians, and impaired spirometry. Multi-disciplinary assessment and comprehensive investigation is needed in clinical practice to address the many factors associated with breathlessness in the population.

Impact of lifetime body mass index trajectories on the incidence and persistence of adult asthma.

BACKGROUND: High body mass index (BMI) trajectories from childhood to adulthood are associated with the development of some chronic diseases, but whether such trajectories influence adult asthma has not been investigated to date. Therefore, we investigated associations between BMI trajectories from childhood to middle age (5-43 years) and incidence, persistence and relapse of asthma from ages 43 to 53 years. METHODS: In the Tasmanian Longitudinal Health Study (n=4194), weight and height were recorded at eight time-points between 5 and 43 years of age. BMI trajectories were developed using group-based trajectory modelling. Associations between BMI trajectories and asthma incidence, persistence and relapse from age 43 to 53 years, bronchial hyperresponsiveness (BHR) at age 50 years, and bronchodilator responsiveness at age 53 years were modelled using multiple logistic and linear regression. RESULTS: Five distinct BMI trajectories were identified: average, low, child high-decreasing, child average-increasing and high. Compared with the average trajectory, child average-increasing and high trajectories were associated with increased risk of incident asthma (OR 2.6, 95% CI 1.1-6.6 and OR 4.4, 95% CI 1.7-11.4, respectively) and BHR in middle age (OR 2.9, 95% CI 1.1-7.5 and OR 3.5, 95% CI 1.1-11.4, respectively). No associations were observed for asthma persistence or relapse. CONCLUSIONS: Participants with child average-increasing and high BMI trajectories from childhood to middle age were at higher risk of incident adult asthma. Thus, encouraging individuals to maintain a normal BMI over the life course may help reduce the burden of adult asthma.

Prevalence of chronic obstructive pulmonary disease with breathlessness in Australia: weighted using the 2016 Australian census.

Access to up-to-date Australian disease prevalence estimates assists health services and consumer organisations to plan and allocate resources. The Burden of Obstructive Lung Disease study was conducted between 2006 and 2012 and provided chronic obstructive pulmonary disease (COPD) (post-bronchodilator airflow limitation) prevalence estimates weighted to the 2006 Australian census. Using the 2016 Australian census, an updated prevalence estimate of all COPD is 8.30% (95% confidence interval = 6.59%-10.01%) for adults aged 40 or more years in Australia and includes 2.52% with mild breathlessness, 0.99% with moderate breathlessness and 0.91% with severe breathlessness.

Childhood pneumonia, pleurisy and lung function: a cohort study from the first to sixth decade of life.

INTRODUCTION: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. METHODS: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. RESULTS: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively). DISCUSSION: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age.

Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a global leading cause of morbidity and mortality, characterised by acute deterioration in symptoms. During these exacerbations, people are prone to developing alveolar hypoventilation, which may be partly caused by the administration of high inspired oxygen concentrations. OBJECTIVES: To determine the effect of different inspired oxygen concentrations ("high flow" compared to "controlled") in the pre-hospital setting (prior to casualty/emergency department) on outcomes for people with acute exacerbations of COPD (AECOPD). SEARCH METHODS: The Cochrane Airways Group Specialised Register, reference lists of articles and online clinical trial databases were searched. Authors of identified randomised controlled trials (RCTs) were also contacted for details of other relevant published and unpublished studies. The most recent search was conducted on 16 September 2019. SELECTION CRITERIA: We included RCTs comparing oxygen therapy at different concentrations or oxygen therapy versus placebo in the pre-hospital setting for treatment of AECOPD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The primary outcome was all-cause and respiratory-related mortality. MAIN RESULTS: The search identified a total of 824 citations; one study was identified for inclusion and two studies are awaiting classification. The 214 participants involved in the included study were adults with AECOPD, receiving treatment by paramedics en route to hospital. The mean age of participants was 68 years. A reduction in pre/in-hospital mortality was observed in favour of the titrated oxygen group (two deaths in the titrated oxygen group compared to 11 deaths in the high-flow control arm; risk ratio (RR) 0.22, 95% confidence interval (CI) 0.05 to 0.97; 214 participants). This translates to an absolute effect of 94 per 1000 (high-flow oxygen) compared to 21 per 1000 (titrated oxygen), and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 12 to 355) with titrated oxygen therapy. Other than mortality, no other adverse events were reported in the included study. Wide confidence intervals were observed between groups for arterial blood gas (though this may be confounded by protocol infidelity in the included study for this outcome measure), treatment failure requiring invasive or non-invasive ventilation or hospital utilisation. No data were reported for quality of life, lung function or dyspnoea. Risk of bias within the included study was largely unclear, though there was high risk of bias in domains relating to performance and attrition bias. We judged the evidence to be of low certainty, according to GRADE criteria. AUTHORS' CONCLUSIONS: The one included study found a reduction in pre/in-hospital mortality for the titrated oxygen arm compared to the high-flow control arm. However, the paucity of evidence somewhat limits the reliability of these findings and generalisability to other settings. There is a need for robust, well-designed RCTs to further investigate the effect of oxygen therapies in the pre-hospital setting for people with AECOPD.

Occupational exposure to solvents and lung function decline: A population based study.

RATIONALE: While cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements. OBJECTIVES: We aimed to investigate the associations between occupational exposures and longitudinal lung function decline in the population-based Tasmanian Longitudinal Health Study. METHODS: Lung function decline between ages 45 years and 50 years was assessed using data from 767 participants. Using lifetime work history calendars completed at age 45 years, exposures were assigned according to the ALOHA plus Job Exposure Matrix. Occupational exposures were defined as ever exposed and cumulative exposure -unit- years. We investigated effect modification by sex, smoking and asthma status. RESULTS: Compared with those without exposure, ever exposures to aromatic solvents and metals were associated with a greater decline in FEV1 (aromatic solvents 15.5 mL/year (95% CI -24.8 to 6.3); metals 11.3 mL/year (95% CI -21.9 to - 0.7)) and FVC (aromatic solvents 14.1 mL/year 95% CI -28.8 to - 0.7; metals 17.5 mL/year (95% CI -34.3 to - 0.8)). Cumulative exposure (unit years) to aromatic solvents was also associated with greater decline in FEV1 and FVC. Women had lower cumulative exposure years to aromatic solvents than men (mean (SD) 9.6 (15.5) vs 16.6 (14.6)), but greater lung function decline than men. We also found association between ever exposures to gases/fumes or mineral dust and greater decline in lung function. CONCLUSIONS: Exposures to aromatic solvents and metals were associated with greater lung function decline. The effect of aromatic solvents was strongest in women. Preventive strategies should be implemented to reduce these exposures in the workplace.

Childhood measles contributes to post-bronchodilator airflow obstruction in middle-aged adults: A cohort study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post-bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post-BD AO through interactions with asthma and/or smoking in a non-immunized middle-aged population. METHODS: The population-based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow-up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post-BD forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC; continuous variable) and AO (FEV1 /FVC < lower limit of normal) were estimated by multiple regression. RESULTS: Sixty-nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack-years on post-BD FEV1 /FVC ratio in middle age (z-score: -0.70 (95% CI: -1.1 to -0.3) vs -1.36 (-1.6 to -1.1), three-way interaction: P = 0.009), especially for those with childhood-onset asthma. For never- and ever-smokers of <10 pack-years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post-BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4-42) vs 2.17 (0.9-5.3)). CONCLUSION: Childhood measles infection appears to compound the associations between smoking, current asthma and post-BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle-aged adults.

Influenza vaccine for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective. OBJECTIVES: To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective. SEARCH METHODS: We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane. MAIN RESULTS: We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.

Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) should be treated with systemic corticosteroid for seven to 14 days. Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could reduce adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven or fewer days) and conventional longer-duration (longer than seven days) systemic corticosteroid treatment of adults with acute exacerbations of COPD. SEARCH METHODS: Searches were carried out using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials) and ongoing trials registers up to March 2017. SELECTION CRITERIA: Randomised controlled trials comparing different durations of systemic corticosteroid defined as short (i.e. seven or fewer days) or longer (i.e. longer than seven days). Other interventions-bronchodilators and antibiotics-were standardised. Studies with participants requiring assisted ventilation were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment. AUTHORS' CONCLUSIONS: Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.

Gefitinib for advanced non-small cell lung cancer.

BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant conference proceedings, clinical trial registries and references lists of retrieved articles. SELECTION CRITERIA: We included trials assessing gefitinib, alone or in combination with other treatment, compared to placebo or other treatments in the first- or successive-line treatment of patients with NSCLC, excluding compassionate use. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodology. Two authors independently assessed the search results to select those with sound methodological quality. We carried out all analyses on an intention-to-treat basis. We recorded the following outcome data: overall survival, progression-free survival, toxicity, tumour response and quality of life. We also collected data for the following subgroups: Asian ethnicity and positive epidermal growth factor receptor (EGFR) mutation. MAIN RESULTS: We included 35 eligible randomised controlled trials (RCTs), which examined 12,089 patients.General populationGefitinib did not statistically improve overall survival when compared with placebo or chemotherapy in either first- or second-line settings. Second-line gefitinib prolonged time to treatment failure (TTF) (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001) when compared with placebo. Maintenance gefitinib improved progression-free survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line therapy.Studies in patients of Asian ethnicity or that conducted subgroup analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66, 95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI 0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in combination with a chemotherapy regimen improved progression-free survival versus either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P = 0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second-line setting, progression-free survival was superior in patients given gefitinib over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71, 95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively). Combining gefitinib with chemotherapy in the second-line setting was superior to gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy, gefitinib improved progression-free survival when compared with placebo (HR 0.42, 95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive tumoursStudies in patients with EGFR mutation-positive tumours showed an improvement in progression-free survival in favour of gefitinib over first-line and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24, 95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy following chemotherapy improved overall and progression-free survival (HR 0.39, 95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001, respectively) in one phase III study when compared to placebo.Toxicities from gefitinib included skin rash, diarrhoea and liver transaminase derangements. Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In terms of quality of life, gefitinib improved Functional Assessment of Cancer Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to 11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P < 0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001) scores when compared with chemotherapy. AUTHORS' CONCLUSIONS: This systematic review shows that gefitinib, when compared with standard first- or second-line chemotherapy or maintenance therapy, probably has a beneficial effect on progression-free survival and quality of life in selected patient populations, particularly those with tumours bearing sensitising EGFR mutations.Patients with EGFR mutations lived longer when given maintenance gefitinib than those given placebo.One study conducted subgroup analysis and showed that gefitinib improved overall survival over placebo in the second-line setting in patients of Asian ethnicity. All other studies did not detect any benefit on overall survival. The data analysed in this review were very heterogenous. We were limited in the amount of data that could be pooled, largely due to variations in study design. The risk of bias in most studies was moderate, with some studies not adequately addressing potential selection, attrition and reporting bias. This heterogeneity may have an impact on the applicability of the resultsCombining gefitinib with chemotherapy appears to be superior in improving progression-free survival to either gefitinib or chemotherapy alone, however further data and phase III studies in these settings are required.Gefitinib has a favourable toxicity profile when compared with current chemotherapy regimens. Although there is no improvement in overall survival, gefitinib compares favourably with cytotoxic chemotherapy in patients with EGFR mutations with a prolongation of progression-free survival and a lesser side effect profile.

Occupational exposure to pesticides are associated with fixed airflow obstruction in middle-age.

RATIONALE: Population-based studies have found evidence of a relationship between occupational exposures and Chronic Obstructive Pulmonary Disease (COPD), but these studies are limited by the use of prebronchodilator spirometry. Establishing this link using postbronchodilator is critical, because occupational exposures are a modifiable risk factor for COPD. OBJECTIVES: To investigate the associations between occupational exposures and fixed airflow obstruction using postbronchodilator spirometry. METHODS: One thousand three hundred and thirty-five participants were included from 2002 to 2008 follow-up of the Tasmanian Longitudinal Health Study (TAHS). Spirometry was performed and lifetime work history calendars were used to collect occupational history. ALOHA plus Job Exposure Matrix was used to assign occupational exposure, and defined as ever exposed and cumulative exposure unit (EU)-years. Fixed airflow obstruction was defined by postbronchodilator FEV1/FVC <0.7 and the lower limit of normal (LLN). Multinomial logistic regressions were used to investigate potential associations while controlling for possible confounders. RESULTS: Ever exposure to biological dust (relative risk (RR)=1.58, 95% CI 1.01 to 2.48), pesticides (RR=1.74,95% CI 1.00 to 3.07) and herbicides (RR=2.09,95% CI 1.18 to 3.70) were associated with fixed airflow obstruction. Cumulative EU-years to all pesticides (RR=1.11,95% CI 1.00 to 1.25) and herbicides (RR=1.15,95% CI 1.00 to 1.32) were also associated with fixed airflow obstruction. In addition, all pesticides exposure was consistently associated with chronic bronchitis and symptoms that are consistent with airflow obstruction. Ever exposure to mineral dust, gases/fumes and vapours, gases, dust or fumes were only associated with fixed airflow obstruction in non-asthmatics only. CONCLUSIONS: Pesticides and herbicides exposures were associated with fixed airflow obstruction and chronic bronchitis. Biological dust exposure was also associated with fixed airflow obstruction in non-asthmatics. Minimising occupational exposure to these agents may help to reduce the burden of COPD.

Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are at increased risk of pneumococcal disease, especially pneumonia, as well as acute exacerbations with associated morbidity and healthcare costs. OBJECTIVES: To determine the efficacy of injectable pneumococcal vaccination for preventing pneumonia in persons with COPD. SEARCH METHODS: We searched the Cochrane Airways COPD Trials Register and the databases CENTRAL, MEDLINE and Embase, using prespecified terms. Searches are current to November 2016. SELECTION CRITERIA: We included randomised controlled trials (RCT) comparing injectable pneumococcal polysaccharide vaccine (PPV) or pneumococcal conjugated vaccine (PCV) versus a control or alternative vaccine type in people with COPD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. For meta-analyses, we subgrouped studies by vaccine type. MAIN RESULTS: For this update, we added five studies (606 participants), meaning that the review now includes a total of 12 RCTs involving 2171 participants with COPD. Average age of participants was 66 years, male participants accounted for 67% and mean forced expiratory volume in one second (FEV1) was 1.2 L (five studies), 54% predicted (four studies). We assessed risks of selection, attrition and reporting bias as low, and risks of performance and detection bias as moderate.Compared with control, the vaccine group had a lower likelihood of developing community-acquired pneumonia (CAP) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.43 to 0.89; six studies, n = 1372; GRADE: moderate), but findings did not differ specifically for pneumococcal pneumonia (Peto OR 0.26, 95% CI 0.05 to 1.31; three studies, n = 1158; GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) (preventing one episode of CAP) was 21 (95% CI 15 to 74). Mortality from cardiorespiratory causes did not differ between vaccine and control groups (OR 1.07, 95% CI 0.69 to 1.66; three studies, n = 888; GRADE: moderate), nor did all-cause mortality differ (OR 1.00, 95% CI 0.72 to 1.40; five studies, n = 1053; GRADE: moderate). The likelihood of hospital admission for any cause, or for cardiorespiratory causes, did not differ between vaccine and control groups. Vaccination significantly reduced the likelihood of a COPD exacerbation (OR 0.60, 95% CI 0.39 to 0.93; four studies, n = 446; GRADE: moderate). The NNTB to prevent a patient from experiencing an acute exacerbation was 8 (95% CI 5 to 58). Only one study (n = 181) compared the efficacy of different vaccine types - 23-valent PPV versus 7-valent PCV - and reported no differences for CAP, all-cause mortality, hospital admission or likelihood of a COPD exacerbation, but investigators described a greater likelihood of some mild adverse effects of vaccination with PPV-23. AUTHORS' CONCLUSIONS: Injectable polyvalent pneumococcal vaccination provides significant protection against community-acquired pneumonia, although no evidence indicates that vaccination reduced the risk of confirmed pneumococcal pneumonia, which was a relatively rare event. Vaccination reduced the likelihood of a COPD exacerbation, and moderate-quality evidence suggests the benefits of pneumococcal vaccination in people with COPD. Evidence was insufficient for comparison of different pneumococcal vaccine types.

The Dose-Response Association between Nitrogen Dioxide Exposure and Serum Interleukin-6 Concentrations.

Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD), and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO2) exposure (as a marker of traffic-related air pollution) and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO) and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389) were analyzed by multivariable logistic regression, using serum interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNF-α) as the outcome. Mean annual NO2 exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV1/FVC) < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001) per quartile increase in NO2). This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO2 and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases.

Mother's smoking and complex lung function of offspring in middle age: A cohort study from childhood.

BACKGROUND AND OBJECTIVE: Existing evidence that supports maternal smoking to be a potential risk factor for chronic obstructive pulmonary disease (COPD) for adult offspring has barely been mentioned in major guideline documents, suggesting a need for more robust and consistent data. We aimed to examine whether such early life exposure can predispose to COPD in middle age, possibly through its interaction with personal smoking. METHODS: The fifth-decade follow-up of the Tasmanian Longitudinal Health Study cohort, which was first studied in 1968 (n = 8583), included a 2004 postal survey (n = 5729 responses) and subsequent laboratory attendance (n = 1389) for comprehensive lung function testing between 2006 and 2008. Multivariable linear and logistic regression models included sampling weights. RESULTS: Post-bronchodilator airflow obstruction (less than fifth percentile) was detected for 9.3% (n = 123) of middle-aged offspring. Its association with heavy maternal smoking (>20 cigarettes/day) during childhood was 2.7-fold higher than for those without exposure (95% confidence interval [1.3, 5.7] P = 0.009). Maternal smoking per se approximately doubled the adverse effect of personal smoking on gas transfer factor (z-score -0.46 [-0.6 to -0.3] vs -0.25 [-0.4 to -0.1], P[interaction] = 0.048) and was paradoxically associated with reduced residual volumes for non-smokers. CONCLUSIONS: Heavy maternal smoking during childhood appears to predispose to spirometrically defined COPD. The interplay between maternal and personal smoking on gas transfer factor suggests that early life exposure increases an individual's susceptibility to adult smoking exposure. These findings provide further evidence to suggest that maternal smoking might be a risk factor for COPD and reinforce the public health message advocating smoking abstinence.

Action plans with brief patient education for exacerbations in chronic obstructive pulmonary disease.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major driver of decline in health status and impose high costs on healthcare systems. Action plans offer a form of self-management that can be delivered in the outpatient setting to help individuals recognise and initiate early treatment for exacerbations, thereby reducing their impact. OBJECTIVES: To compare effects of an action plan for COPD exacerbations provided with a single short patient education component and without a comprehensive self-management programme versus usual care. Primary outcomes were healthcare utilisation, mortality and medication use. Secondary outcomes were health-related quality of life, psychological morbidity, lung function and cost-effectiveness. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register along with CENTRAL, MEDLINE, Embase and clinical trials registers. Searches are current to November 2015. We handsearched bibliographic lists and contacted study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCT) and quasi-RCTs comparing use of an action plan versus usual care for patients with a clinical diagnosis of COPD. We permitted inclusion of a single short education component that would allow individualisation of action plans according to management needs and symptoms of people with COPD, as well as ongoing support directed at use of the action plan. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. For meta-analyses, we subgrouped studies via phone call follow-up directed at facilitating use of the action plan. MAIN RESULTS: This updated review includes two additional studies (and 976 additional participants), for a total of seven parallel-group RCTs and 1550 participants, 66% of whom were male. Participants' mean age was 68 years and was similar among studies. Airflow obstruction was moderately severe in three studies and severe in four studies; mean post bronchodilator forced expiratory volume in one second (FEV1) was 54% predicted, and 27% of participants were current smokers. Four studies prepared individualised action plans, one study an oral plan and two studies standard written action plans. All studies provided short educational input on COPD, and two studies supplied ongoing support for action plan use. Follow-up was 12 months in four studies and six months in three studies.When compared with usual care, an action plan with phone call follow-up significantly reduced the combined rate of hospitalisations and emergency department (ED) visits for COPD over 12 months in one study with 743 participants (rate ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.79; high-quality evidence), but the rate of hospitalisations alone in this study failed to achieve statistical significance (RR 0.69, 95% CI 0.47 to 1.01; moderate-quality evidence). Over 12 months, action plans significantly decreased the likelihood of hospital admission (odds ratio (OR) 0.69, 95% CI 0.49 to 0.97; n = 897; two RCTs; moderate-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) 19 (11 to 201)) and the likelihood of an ED visit (OR 0.55, 95% CI 0.38 to 0.78; n = 897; two RCTs; moderate-quality evidence; NNTB over 12 months 12 (9 to 26)) compared with usual care.Results showed no significant difference in all-cause mortality during 12 months (OR 0.88, 95% CI 0.59 to 1.31; n = 1134; four RCTs; moderate-quality evidence due to wide confidence interval). Over 12 months, use of oral corticosteroids was increased with action plans compared with usual care (mean difference (MD) 0.74 courses, 95% CI 0.12 to 1.35; n = 200; two RCTs; moderate-quality evidence), and the cumulative prednisolone dose was significantly higher (MD 779.0 mg, 95% CI 533.2 to 10248; n = 743; one RCT; high-quality evidence). Use of antibiotics was greater in the intervention group than in the usual care group (subgrouped by phone call follow-up) over 12 months (MD 2.3 courses, 95% CI 1.8 to 2.7; n = 943; three RCTs; moderate-quality evidence).Subgroup analysis by ongoing support for action plan use was limited; review authors noted no subgroup differences in the likelihood of hospital admission or ED visits or all-cause mortality over 12 months. Antibiotic use over 12 months showed a significant difference between subgroups in studies without and with ongoing support.Overall quality of life score on St George's Respiratory Questionnaire (SGRQ) showed a small improvement with action plans compared with usual care over 12 months (MD -2.8, 95% CI -0.8 to -4.8; n = 1009; three RCTs; moderate-quality evidence). Low-quality evidence showed no benefit for psychological morbidity as measured with the Hospital Anxiety and Depression Scale (HADS). AUTHORS' CONCLUSIONS: Use of COPD exacerbation action plans with a single short educational component along with ongoing support directed at use of the action plan, but without a comprehensive self-management programme, reduces in-hospital healthcare utilisation and increases treatment of COPD exacerbations with corticosteroids and antibiotics. Use of COPD action plans in this context is unlikely to increase or decrease mortality. Whether additional benefit is derived from periodic ongoing support directed at use of an action plan cannot be determined from the results of this review.

Prevalence of airflow obstruction and reduced forced vital capacity in an Aboriginal Australian population: The cross-sectional BOLD study.

BACKGROUND AND OBJECTIVE: Mortality and hospital separation data suggest a higher burden of chronic obstructive pulmonary disease (COPD) in indigenous than non-indigenous subpopulations of high-income countries. This study sought to accurately measure the true prevalence of post-bronchodilator airflow obstruction and forced vital capacity reduction in representative samples of Indigenous and non-Indigenous Australians. METHODS: This study applies cross-sectional population-based survey of Aboriginal and non-Indigenous residents of the Kimberley region of Western Australia aged 40 years or older, following the international Burden Of Lung Disease (BOLD) protocol. Quality-controlled spirometry was conducted before and after bronchodilator. COPD was defined as Global initiative for chronic Obstructive Lung Disease (GOLD) Stage 2 and above (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) ratio <0.7 and FEV1 < 80% predicted). RESULTS: Complete data were available for 704 participants. The prevalence of COPD, adjusted for age, gender and body weight in Aboriginal participants (7.2%, 95% confidence interval (CI) 3.9 to 10.4) was similar to that seen in non-Indigenous Kimberley participants (8.2%, 95% CI 5.7 to 10.7) and non-Indigenous residents of the remainder of Australia (7.1%, 95% CI 6.1 to 8.0). The prevalence of low FVC (<80% predicted) was substantially higher in Aboriginal compared with non-Indigenous participants (74.0%, 95% CI 69.1 to 78.8, vs 9.7%, 95% CI 7.1 to 12.4). CONCLUSIONS: Low FVC, rather than airflow obstruction, characterizes the impact of chronic lung disease previously attributed to COPD in this population subject to significant social and economic disadvantage. Environmental risk factors other than smoking as well as developmental factors must be considered. These findings require further investigation and have implications for future prevention of chronic lung disease in similar populations.

Indacaterol, a once-daily beta2-agonist, versus twice-daily beta2-agonists or placebo for chronic obstructive pulmonary disease.

BACKGROUND: Indacaterol is an inhaled long-acting beta2-agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain. OBJECTIVES: To compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting beta2-agonists for the treatment of patients with stable COPD. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014. SELECTION CRITERIA: We included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting beta2-agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD. DATA COLLECTION AND ANALYSIS: Two review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC). MAIN RESULTS: A total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data that could be used in this review. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12 weeks and 52 weeks in duration. Overall the quality of the evidence was strong, and risk of significant bias was minimal in most of the included studies. Enrolled participants had stable COPD across a range of spirometric severities. Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80% predicted, and a mean FEV1 of approximately 50% was predicted in most studies. Patients with concurrent respiratory disease, including asthma, were excluded. Concomitant use of inhaled corticosteroids was permitted.The primary objectives were to compare trough FEV1 at the end of dosing, exacerbation rates and quality of life. Significant adverse events, mortality and dyspnoea were included as secondary outcomes. Compared with placebo, a significant and clinically relevant improvement in trough FEV1 was noted with indacaterol (mean difference (MD) 149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared with placebo, a significant improvement in mean St George Respiratory Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the proportion of participants experiencing clinically relevant improvement in SGRQ score was significantly greater (odds ratio (OR) 1.63, 95% CI 1.46 to 1.84). Compared with twice-daily beta2-agonists, a small but statistically significant increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to 82.17). Differences between indacaterol and twice-daily beta2-agonists in mean SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of participants achieving clinically relevant improvements in SGRQ scores (OR 1.07, 95% CI 0.87 to 1.32) were not statistically significant, but the confidence intervals are too wide to permit the conclusion that the treatments were equivalent. Data were insufficient for analysis of differences in exacerbation rates for both placebo and twice-daily beta2-agonist comparisons. AUTHORS' CONCLUSIONS: For patients with stable COPD, use of indacaterol versus placebo results in statistically significant and clinically meaningful improvements in lung function and quality of life. The clinical benefit for lung function is at least as good as that seen with twice-daily long-acting beta2-agonists. The comparative effect on quality of life remains uncertain, as important differences cannot be excluded.

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH METHODS: We searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually. MAIN RESULTS: A total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.